Obiettivo Creating true molecular complexity in a modular, combinatorial fashion is one of the great visions in applied enzymology and chemistry. Nature achieves this feat by using modular biosynthetic enzymes. These microbial proteins generate many of the most important natural products of therapeutic value, including antiinfective, anticancer, and immunosuppressive agents. To construct such compounds, each enzyme module incorporates and often modifies one building block in an assembly line-like process. Among the known modular enzymes, the recently discovered trans-acyltransferase polyketide synthases (trans-AT PKSs) exhibit an unparalleled biosynthetic diversity and tendency to form extensively mosaic-like hybrid enzymes during evolution. As a consequence, many bioactive polyketides generated by these enzymes exhibit combinatorial-like hybrid structures. This phenomenon provides unprecedented opportunities to understand the evolution of metabolic complexity and to apply these principles to metabolic engineering through parts-based synthetic biology. SynPlex will use a novel hypothesis-driven, multi-faceted strategy to interrogate and utilize the distinct combinatorial properties and metabolic richness of trans-AT PKSs. This multidisciplinary project aims to (i) unravel principles of how mosaic PKSs and their metabolites are formed in Nature, (ii) characterize non-canonical PKS components, (iii) create a toolbox of PKS parts for synthetic biology based on these evolutionary and biochemical principles, and (iv) harness the combinatorial potential of trans-AT systems to access complex natural as well as non-natural products. This innovative concept that merges evolutionary biology, enzymology, synthetic biology, and chemistry will result in a broad understanding of these most complex of all known proteins. It has the potential to provide generic, robust synthetic biology platforms to engineer complex polyketides with a wide range of features in a predictable way. Campo scientifico engineering and technologyindustrial biotechnologymetabolic engineeringnatural sciencesbiological sciencessynthetic biologynatural sciencesbiological sciencesevolutionary biologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Programma(i) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Argomento(i) ERC-2016-ADG - ERC Advanced Grant Invito a presentare proposte ERC-2016-ADG Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-ADG - Advanced Grant Istituzione ospitante EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH Contribution nette de l'UE € 2 495 755,00 Indirizzo Raemistrasse 101 8092 Zuerich Svizzera Mostra sulla mappa Regione Schweiz/Suisse/Svizzera Zürich Zürich Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 2 495 755,00 Beneficiari (1) Classifica in ordine alfabetico Classifica per Contributo netto dell'UE Espandi tutto Riduci tutto EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH Svizzera Contribution nette de l'UE € 2 495 755,00 Indirizzo Raemistrasse 101 8092 Zuerich Mostra sulla mappa Regione Schweiz/Suisse/Svizzera Zürich Zürich Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 2 495 755,00
